Objective Investigate the potential correlation between the age of initial sexual contact, the lifetime accumulation of sexual partners, and the occurrence of intracranial aneurysm (IA) employing a two-sample Mendelian randomization approach.Methods This research aims to elucidate the causal relationship between intracranial aneurysm (IA) and sexual variables. Two distinct sexual variables, specifically the age had first sexual intercourse (n = 406,457) and the lifetime number of sexual partners (n = 378,882), were employed as representative parameters in a two-sample Mendelian randomization (MR) study. Outcome data from 23 cohorts, comprising 5,140 cases and 71,934 controls, were gathered through genome-wide association studies (GWAS). To bolster analytical rigor, five distinct methodologies were applied, encompassing MR-Egger technique, weighted median, inverse variance weighted, simple modeling, and weighted modeling.Results Our investigation unveiled a causal relationship between the age first had sexual intercourse and the occurrence of intracranial aneurysm (IA), employing the Inverse Variance Weighted (IVW) approach [Odds Ratio (OR): 0.609, p-value: 5.684E-04, 95% Confidence Interval (CI): 0.459-0.807]. This association was notably significant in the context of unruptured intracranial aneurysms (uIA) using the IVW approach (OR: 0.392, p-value: 6.414E-05, 95% CI: 0.248-0.621). Conversely, our findings did not reveal any discernible link between the lifetime number of sexual partners and the occurrence of IA (IA group: OR: 1.346, p-value: 0.415, 95% CI: 0.659-2.749; SAH group: OR: 1.042, p-value: 0.943, 95% CI: 0.338-3.209; uIA group: OR: 1.990, p-value: 0.273, 95% CI: 0.581-6.814).Conclusion The two-sample Mendelian Randomization (MR) study presented herein provides evidence supporting a correlation between the age of initial engagement in sexual activity and the occurrence of intracranial aneurysm (IA), with a noteworthy emphasis on unruptured intracranial aneurysms (uIA). Nevertheless, our investigation failed to establish a definitive association between IA and the cumulative lifetime number of sexual partners.
